Abstract A67: The effects of SAHA and EGCG on metastatic potential in triple-negative breast cancer

Abstract

Abstract Approximately 12% of breast cancers are triple negative, and are nearly two times more common in black women that white women. These cancers have a poorer short-term prognosis than other types due to the lack of targeted therapies. The purpose of this study was to use suberoylanilide hydroxamic acid (SAHA), a histone deacetylase (HDAC) inhibitor used to treat cutaneous T cell lymphoma (CTCL), and epigallocatechin-3-gallate (EGCG), a DNA methyltransferase (DNMT) inhibitor found in green tea, to decrease metastatic potential in triple-negative breast cancer (TNBC) cells. SAHA and EGCG were administered singly and in combination to determine if the combination was more efficacious than either compound alone in their effects on cell viability and foci, or colony, formation. RNA and protein analysis was performed to evaluate epithelial versus mesenchymal markers, while scratch tests provided phenotypic evidence of changes in migration capability. We found that the combination of SAHA and EGCG at optimal concentrations of 3 μM SAHA and 5 μM reduced breast cancer cellular viability in an additive manner while this combination had no significant effect on control breast cells. This is a very low dose of EGCG compared to most anticancer studies. The colonies formed by the breast cancer cells decreased in size and number. Interestingly, EGCG administered singly increased colony formation. The combination of SAHA and EGCG also reactivated estrogen receptor alpha (ERα), and decreased the expression of miR-221/222, which are microRNAs involved in migration and invasion. The scratch tests supported these findings, with the breast cancer cells exhibiting a decreased ability to migrate. These findings demonstrate the abilities of combined SAHA and EGCG to decrease metastatic potential through epigenetic mechanisms in TNBC. Citation Format: Kayla Ashlyn Lewis, Trygve O. Tollefsbol. The effects of SAHA and EGCG on metastatic potential in triple-negative breast cancer [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr A67.